title: Synthesis and in vitro cellular evaluation of novel anti-tumor norcantharidin-conjugated chitosan derivatives.
abstract: Norcantharidin-conjugated chitosan conjugates (NCTD-CSs) with different degrees of substitution (DS, 60.2% and 97.9%) were synthesized and characterized by (1)H NMR, FT-IR, and XRD. In comparison with CS, the NCTD-CSs had lower crystallinity and better water solubility. Less than 6% NCTD was released from the NCTD-CSs through the hydrolysis of ester bonds in phosphate-buffered solution (PBS, pH 5.0 and 7.4) within 16 days, showing sustained drug release characteristic. The result of cytoxicity study showed that the NCTD-CSs were cytotoxic to MGC80-3 cells and their cytotoxicity was lower than that of NCTD. Fluorescence microscope and flow cytometry analysis demonstrated that the amount of the NCTD-CSs uptaken by MGC80-3 cells increased as incubation time. Confocal microscopy study showed that the NCTD-CSs were internalized into cells by endocytosis and mainly localized in lysosomes within 24h. It was found that the NCTD-CSs arrested MGC80-3 cell cycle at G2/M phase and induced cell death via cell apoptosis similarly to NCTD. These results indicated that the NCTD-CSs might be an efficient NCTD delivery system for cancer therapy.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China; State Key Laboratory of Dairy Biotechnology, Institute of Bright Dairy & Food Co., Ltd., 1518 Jiangchangxi Road, Shanghai 200436, PR China.
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Xu
authors.forename: Yanggong
authors.initials: Y
authors.lastname: Li
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shen
authors.forename: Shengrong
authors.initials: S
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004337:Drug Carriers; C069741:norcantharidin; D048271:Chitosan
keywords: Cellular evaluation; Conjugates; Drug release